Synthesis, 68Ga labeling and preliminary evaluation of DOTA peptide binding vascular adhesion protein-1: a potential PET imaging agent for diagnosing osteomyelitis

Ujula, Tiina; Salomäki, Satu; Virsu, Pauliina; Lankinen, Petteri; Mäkinen, Tatu J.; Autio, Anu; Yegutkin, Gennady G.; Knuuti, Juhani; Jalkanen, Sirpa; Roivainen, Anne

doi:10.1016/j.nucmedbio.2009.04.008

« Previous Next »Nuclear Medicine and Biology
Volume 36, Issue 6 , Pages 631-641, August 2009

Synthesis, ⁶⁸Ga labeling and preliminary evaluation of DOTA peptide binding vascular adhesion protein-1: a potential PET imaging agent for diagnosing osteomyelitis

Tiina Ujula
- Turku PET Center, Turku University Hospital, Turku, Finland
Satu Salomäki
- Turku PET Center, Turku University Hospital, Turku, Finland
- Department of Chemistry, University of Turku, Turku, Finland
Pauliina Virsu
- Turku PET Center, Turku University Hospital, Turku, Finland
Petteri Lankinen
- Orthopedic Research Unit, University of Turku, Turku, Finland
Tatu J. Mäkinen
- Orthopedic Research Unit, University of Turku, Turku, Finland
Anu Autio
- Turku PET Center, Turku University Hospital, Turku, Finland
Gennady G. Yegutkin
- MediCity Research Laboratory, University of Turku, Turku, Finland
Juhani Knuuti
- Turku PET Center, Turku University Hospital, Turku, Finland
Sirpa Jalkanen
- MediCity Research Laboratory, University of Turku, Turku, Finland
- National Public Health Institute, Turku, Finland
Anne Roivainen
- Turku PET Center, Turku University Hospital, Turku, Finland
- Turku Center for Disease Modeling, University of Turku, Turku, Finland
- Corresponding author. Turku PET Center, Turku University Hospital, FI-20521 Turku, Finland. Tel.: +358 2 3132862; fax: +358 2 2318191.

Received 23 February 2009; received in revised form 18 March 2009; accepted 6 April 2009.

Abstract

Introduction

Vascular adhesion protein-1 (VAP-1) is an infection/inflammation-inducible endothelial glycoprotein. Based on our previous studies, the most VAP-1-selective peptide (VAP-P1) was 1,4,7,10-tetraazacyclododecane-N′,N″,N‴,N⁗-tetraacetic acid (DOTA)-conjugated, ⁶⁸gallium (⁶⁸Ga)-labeled (named [⁶⁸Ga]DOTAVAP-P1) and evaluated preliminarily.

Methods

Targeting was evaluated by using VAP-1-transfected cells. Biodistribution of [⁶⁸Ga]DOTAVAP-P1 was studied by positron emission tomography imaging of healthy rats and rats with bone inflammation caused by Staphylococcus aureus infection. Uptake of [⁶⁸Ga]DOTAVAP-P1 in osteomyelitis was compared with negative control peptide and competition with an excess of unlabeled DOTAVAP-P1.

Results

[⁶⁸Ga]DOTAVAP-P1 bound more efficiently to VAP-1-transfected cells than to controls. In rats, [⁶⁸Ga]DOTAVAP-P1 cleared rapidly from blood circulation, excreted quickly in urine and showed an in vivo half-life of 26±2.3 min. Imaging of osteomyelitis demonstrated modest target-to-background ratio. Studies with the negative control peptide and competitors revealed a significantly lower uptake at the infection site compared to [⁶⁸Ga]DOTAVAP-P1.

Conclusions

The results represent a proof-of-concept that infection-induced VAP-1 can be targeted by [⁶⁸Ga]DOTA peptide. [⁶⁸Ga]DOTAVAP-P1 is just the first candidate peptide and an essential opening for developing VAP-1-specific imaging agents.

Keywords: ⁶⁸Gallium, Positron emission tomography, Experimental osteomyelitis, Vascular adhesion protein-1, DOTA peptide, Infection